To the Editor: The recent Lown Right Care article appropriately cautions against aggressive treatment to achieve A1C targets below 7% in older adults with diabetes.1 I suggest an additional step: clinicians should critically evaluate whether an elevated A1C reflects true dysglycemia before making a diagnosis or initiating treatment.
A1C is influenced not only by glycemia but also erythrocyte lifespan and interindividual variation in glycation rates, both of which can alter A1C independent of average blood glucose levels.2–4 In patients with a low pretest probability of hyperglycemia, these factors can produce misleading A1C elevations.
I encountered an athletic 75-year-old woman with an A1C of 6% who was labeled as having prediabetes. Although this value technically fell within the American Diabetes Association range for prediabetes, the association acknowledges that A1C is unreliable as a diagnostic tool when erythrocyte dynamics or glycation rates are altered, urges diagnostic caution in such circumstances, and recommends using plasma glucose criteria instead.4 Her fasting glucose was 88 mg/dL (4.9 mmol/L).
Additional pertinent findings included a triglyceride level of 50 mg/dL (0.56 mmol/L), high-density lipoprotein cholesterol level of 95 mg/dL (2.46 mmol/L) with a triglyceride to high-density lipoprotein ratio of 0.5, waist circumference of 27 inches (69 cm), body mass index of 20.6 kg/m2, and blood pressure of 118/60 mm Hg. This phenotype reflects high insulin sensitivity, with an exceptionally favorable triglyceride to high-density lipoprotein ratio, and is inconsistent with metabolic syndrome, pathologic dysglycemia, or insulin resistance.5,6
The patient's borderline-high hematocrit level of 45.2% and low-normal red cell distribution width of 12.2% were consistent with longer erythrocyte lifespan, a known contributor to misleadingly elevated A1C.2–4 Despite these findings and her normal body mass index, she had been advised to lose weight and that pharmacotherapy, including insulin, might be required. In older adults with normal body mass index, weight loss may increase the risk of osteopenia, sarcopenia, frailty, and falls, whereas glucose-lowering therapy (especially insulin) carries well-established risks without demonstrated patient-oriented benefit at this level of glycemia.1 This cascade—nonindicated testing, misinterpretation, overdiagnosis, and potential overtreatment—is preventable.
When interpreting A1C, as with any laboratory test, the entire clinical context should be considered. When a result is discordant with the clinical picture, a false-positive result should be considered before assigning a diagnosis with its attendant anxiety, diagnostic cascades, and potential harms.
Editor’s Note: This letter was sent to the authors of “Intensive
Glucose Control in Older Patients With Diabetes,” who declined
to reply.
